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Macular EdemaNCT05976139

Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies

A study testing subthreshold treatment with micropulsed laser in people with Macular Edema and Inherited Retinal Dystrophy, run by Fondazione G.B. Bietti, IRCCS at 1 site in Italy.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The purpose of this study is to investigate whether subthreshold treatment with micropulsed laser can be effective in resolving macular edema in patients with inherited retinal dystrophy. Visits will be performed after 1, 3, 6, 9, 12, 18, and 24 months after treatment. Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
subthreshold treatment with micropulsed laser
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteItaly
Study dates
6 Sep 2023to 30 Jul 2025
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with inherited retinal disease
  • Age between 18 and 80 years
  • Conclusive molecular genetic study for IRD
  • Male or female patient
  • Presence of macular oedema assessed by sd-OCT with reduction ≤ 20% after 3 months of diuretics or draining supplements or 4 months after last anti-VEGF or steroid injection
  • Phakic and pseudophakic patients
Show all 9Show fewer
  • Central Retinal thickness > 320 microns in men and > 305 microns in women
  • Informed consent freely granted and acquired before the start of the study
  • Participant has the ability to understand and willingness to follow study instructions and is likely to complete all required visits and procedures.

Who cannot join

  • Patients with cataract extraction prior to 6 months
  • Patients with IOP ≥ 20 mmHg
  • Patients with a clinical diagnosis of retinal dystrophy of unproven genetic origin
  • Patients with diabetes
  • Patients with central serous chorioretinosis, retinal vein occlusion, age-related degeneration
  • Patients with current or previous vitreo-retinal pathology or with indication for vitreo-retinal surgical therapy (tractional oedema)
  • Patients with a lack of target fixation at 32 cm
  • Pregnant women

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Lucia Ziccardi, MD, PhD contact

+390684009486

neuger@fondazionebietti.it

Federica Petrocchi, Orthoptist contact

+390684009486

neuger@fondazionebietti.it

Italy1 site, 1 recruiting
  • IRCSS Fondazione G:B:Bietti

    Rome, RM, 00194

    Lucia Ziccardi, MD, PhD, +390684009486, neuger@fondazionebietti.it

    Federica Petrocchi, Orthoptist, +390684009486, neuger@fondazionebietti.it

    Recruiting

Other trials in Italy

About this study

Official title: Treatment of Macular Oedema in Patients With Hereditary Retinal Dystrophies by Applying the Micropulsed Subthreshold Laser

The purpose of this study is to investigate whether subthreshold treatment with micropulsed laser can be effective in resolving macular edema in patients with inherited retinal dystrophy.

Visits will be performed after 1, 3, 6, 9, 12, 18, and 24 months after treatment. Laser treatment will be performed on the day of the first visit, and its repetition at subsequent visits between months 3 and 12 will be evaluated.

Evaluations of treatment effects will include:

  • comprehensive ophthalmologic examination
  • multifocal electroretinogram
  • OCT examination
  • OCT-angiography examination
  • retinography

Primary endpoint.

  • central retinal thickness, measured by OCT
Read the detailed description

BACKGROUND:

Degenerative diseases of the visual system classified as rare and, in particular, those affecting the retina (known as Inherited retinal dystrophies, IRDs) cause very severe functional deficits. Their onset is in many cases particularly early with a consequent visual impact of extreme severity. They constitute a heterogeneous group from a clinical point of view, but in all of them the loss of photoreceptors causes progressive vision loss that can result in complete blindness.

These pathologies can be complicated by the presence of cataracts, epiretinal membrane and macular oedema (10-50%), resulting in a worsening of visual acuity. While surgical treatment is applicable for the first two complications, the treatment of macular oedema can make use of several options. Oral or topical diuretics (Acetazolamide) are still the first therapeutic approach and, if oedema persists despite treatment, intravitreal corticosteroid injection has been used in various reports. The injection of anti-Vascular Endothelial Growth Factor (VEGF) drugs and vitrectomy have also been proposed but with conflicting results. The use of topical non-steroidal drugs has been studied and proven to be valuable, although inferior to diuretic treatment in terms of visual recovery. The use of intravitreal corticosteroids is also not without possible further complications such as ocular hypertension and early onset of cataracts.

Despite some improvement in retinal oedema by taking the above-mentioned diuretics, relapses can be observed at the end of therapy, reason for taking longer periods (>12 weeks) of therapy. However, the same chronic continuation of diuretic therapy is not always desirable considering its possible adverse events such as tingling sensation, malaise, altered taste sensation and gastrointestinal disorders.

RATIONALE:

The application of the micropulsed subthreshold retinal laser to reduce retinal oedema in various diseases (diabetic oedema, central serous chorioretinopathy, age-related macular degeneration and retinal vein occlusion) has recently gained wide acceptance.

Retinal threshold refers to the tendency of the laser to cause tissue bleaching resulting in retinal cell death, the term sub-threshold implies that the laser uses such a small amount of energy that it does not cause irreversible damage to retinal structures. The term 'micropulsed' derives from the fact that the laser does not use a continuous wave but has a sub-100% duty cycle and the use of 'off' times is what distinguishes this type of laser from conventional lasers and allows the tissue to cool down, preventing laser-induced retinal damage.

The main characteristics of this type of laser are therefore that it does not cause visible retinal damage and that it has therapeutic effects.

One theory of how this type of laser works is through the action of the molecular protective mechanisms of the Heat Shock Protein (Hsp) family in the retina, including protein chaperone activity, stabilisation of the cytoskeleton and prevention of apoptosis mainly through inhibition of cytochrome C release through the phenomenon of 'resetting'. Another theory hypothesized the activation of leucocyte recruitment or remodeling of the extracellular matrix in the choroid and retina. Possible mechanisms of increased trophic factors (CNTF and FGF-2)14 and up-regulation of other factors (MMP-2, MMP-3, TNFα and Nos2) are covered.

TRIAL DESIGN:

Prospective, interventional, single-centre, open-label study involving consecutive enrolment (see sample size in section "Statistics") of patients with macular oedema in retinal dystrophies.

Each patient referred to the Outpatient Clinical and Research Center of Neuro-ophthalmology and Genetic and Rare Diseases with IRD and macular oedema treated for 3 months with diuretics and draining food supplements and without improvement of macular oedema or increase of the same (reduction of post-therapy CRT ≤20% compared to pre-therapy CRT) will be duly informed about the therapeutic option of this study protocol. After verification of the criteria for inclusion in the study and after signing of the informed consent, the patient will be considered eligible for treatment with micropulsed laser by the physicians of the Clinical and Research Center of Neuro-ophthalmology and Genetic and Rare Diseases and Medical Retina. The patient enrolled in the study will be clinically analysed with the instrumentation indicated below at regular intervals (screening/baseline, follow-up 1 [FU1] (1 month), FU2 (3 months), FU3 (6 months), FU4 (9 months), FU5 (12 months), FU6 (18 months) and FU7 (24 months).

Being tested
subthreshold treatment with micropulsed laser
Keywords
Visual Acuity, Retinal Function, IRD, Macular Edema
Medical subject headings
Macular Edema

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • subthreshold treatment with micropulsed laserDevice

    The laser instrument used is the Q 577® Laser System, Iridex, wavelength 577 yellow. The standard pattern used is:

    • Power: 5% Duty Cycle
    • Power 250 mw
    • Pulse duration 200 ms
    • Spot size 100 micron
    • Pattern spacing 0.0 confluente, griglie 7x7
Study groups in NCT05976139
Study groupRoleWhat they receive
inherited retinal dystrophies with macular oedemaExperimentalLaser treatment will be performed in patients with macular edema in IRD (experimental arm) who: * underwent treatment with diuretics or nutritional drainage products for 3 months and subsequent 'wash-out' of one month 17,18 and had no reduction in macular oedema, in terms of central retinal thickness, of at least 20% compared with the initial assessment * they have had an intravitreal injection of anti-VEGF or steroids, and after 3 months there is no reduction in central retinal thickness (CRT) of at least 20% compared to the initial assessment * have after 3 months a thickness reduction <10% compared to baseline assessment, following initial treatment with micropulsed laser, and may be candidates for repeating treatment; * are not eligible for diuretic therapy due to the presence of comorbidities.
Receives: Device: subthreshold treatment with micropulsed laser

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. assessment of significative change in retinal oedema compared to baseline

    assessment of central retinal thickness by macular SD-OCT

    Measured: up to 24 months

Secondary outcomes (3)
  1. To study changes in visual acuity between before and after treatment

    LogMAr visual acuity values

    Measured: up to 24 months

  2. To study the retinal function in the macular area before and after treatment.

    response amplitude density, measured in nV/dg2 and analysed using multifocal electroretinogram, assessing the amplitude in 5 concentric rings centred on the fovea.

    Measured: up to 24 months

  3. To study the retinal perfusion of the macular area by OCT-angiography before and after treatment.

    vascular density (expressed as Retinal Vessel Density) before and after treatment, using OCT-angiography

    Measured: up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Aug 2023
  2. Study start6 Sep 2023
  3. Primary completion30 Jul 2025 (estimated)
  4. Study completion30 Jul 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
10 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05976139
Sponsor's protocol ID
Neu 01-23
Status last verified
Feb 2025
First submitted
19 Jul 2023
Last updated
28 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: At the end of the research, within 6 months after the end of the study, a Final Clinical Report of the study containing clinical comments based on the data generated by the statistical processing will be prepared by the Investigator and/or delegated person. This report will be structured as an \&#34;integrated statistical clinical report\&#34; containing the clinical comments based on the data generated by the statistical report.

Publications

  • Olivares-Gonzalez L, Velasco S, Campillo I, Rodrigo R. Retinal Inflammation, Cell Death and Inherited Retinal Dystrophies. Int J Mol Sci. 2021 Feb 20;22(4):2096. doi: 10.3390/ijms22042096.

    PubMed 33672611
  • Bakthavatchalam M, Lai FHP, Rong SS, Ng DS, Brelen ME. Treatment of cystoid macular edema secondary to retinitis pigmentosa: a systematic review. Surv Ophthalmol. 2018 May-Jun;63(3):329-339. doi: 10.1016/j.survophthal.2017.09.009. Epub 2017 Oct 5.

    PubMed 28987613
  • Hong Y, Li H, Sun Y, Ji Y. A Review of Complicated Cataract in Retinitis Pigmentosa: Pathogenesis and Cataract Surgery. J Ophthalmol. 2020 Dec 21;2020:6699103. doi: 10.1155/2020/6699103. eCollection 2020.

    PubMed 33489339
  • Ikeda Y, Yoshida N, Murakami Y, Nakatake S, Notomi S, Hisatomi T, Enaida H, Ishibashi T. Long-term Surgical Outcomes of Epiretinal Membrane in Patients with Retinitis Pigmentosa. Sci Rep. 2015 Aug 13;5:13078. doi: 10.1038/srep13078.

    PubMed 26268934
  • Sahel J, Bonnel S, Mrejen S, Paques M. Retinitis pigmentosa and other dystrophies. Dev Ophthalmol. 2010;47:160-167. doi: 10.1159/000320079. Epub 2010 Aug 10.

    PubMed 20703049
  • Lemos Reis RF, Moreira-Goncalves N, Estrela Silva SE, Brandao EM, Falcao-Reis FM. Comparison of topical dorzolamide and ketorolac treatment for cystoid macular edema in retinitis pigmentosa and Usher's syndrome. Ophthalmologica. 2015;233(1):43-50. doi: 10.1159/000368052. Epub 2014 Nov 26.

    PubMed 25428176
  • Orzalesi N, Pierrottet C, Porta A, Aschero M. Long-term treatment of retinitis pigmentosa with acetazolamide. A pilot study. Graefes Arch Clin Exp Ophthalmol. 1993 May;231(5):254-6. doi: 10.1007/BF00919100.

    PubMed 8319913
  • Moore SM, Chao DL. Application of subthreshold laser therapy in retinal diseases: a review. Expert Rev Ophthalmol. 2018;13(6):311-320. doi: 10.1080/17469899.2018.1555035. Epub 2018 Dec 11.

    PubMed 31692951
  • Franklin TB, Krueger-Naug AM, Clarke DB, Arrigo AP, Currie RW. The role of heat shock proteins Hsp70 and Hsp27 in cellular protection of the central nervous system. Int J Hyperthermia. 2005 Aug;21(5):379-92. doi: 10.1080/02656730500069955.

    PubMed 16048836
  • Caballero S, Kent DL, Sengupta N, Li Calzi S, Shaw L, Beli E, Moldovan L, Dominguez JM 2nd, Moorthy RS, Grant MB. Bone Marrow-Derived Cell Recruitment to the Neurosensory Retina and Retinal Pigment Epithelial Cell Layer Following Subthreshold Retinal Phototherapy. Invest Ophthalmol Vis Sci. 2017 Oct 1;58(12):5164-5176. doi: 10.1167/iovs.16-20736.

    PubMed 29049716
  • Chidlow G, Shibeeb O, Plunkett M, Casson RJ, Wood JP. Glial cell and inflammatory responses to retinal laser treatment: comparison of a conventional photocoagulator and a novel, 3-nanosecond pulse laser. Invest Ophthalmol Vis Sci. 2013 Mar 28;54(3):2319-32. doi: 10.1167/iovs.12-11204.

    PubMed 23439603
  • Flaxel C, Bradle J, Acott T, Samples JR. Retinal pigment epithelium produces matrix metalloproteinases after laser treatment. Retina. 2007 Jun;27(5):629-34. doi: 10.1097/01.iae.0000249561.02567.fd.

    PubMed 17558327
  • Chalam KV, Bressler SB, Edwards AR, Berger BB, Bressler NM, Glassman AR, Grover S, Gupta SK, Nielsen JS; Diabetic Retinopathy Clinical Research Network. Retinal thickness in people with diabetes and minimal or no diabetic retinopathy: Heidelberg Spectralis optical coherence tomography. Invest Ophthalmol Vis Sci. 2012 Dec 13;53(13):8154-61. doi: 10.1167/iovs.12-10290.

    PubMed 23132803
  • Elman MJ, Bressler NM, Qin H, Beck RW, Ferris FL 3rd, Friedman SM, Glassman AR, Scott IU, Stockdale CR, Sun JK; Diabetic Retinopathy Clinical Research Network. Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2011 Apr;118(4):609-14. doi: 10.1016/j.ophtha.2010.12.033.

    PubMed 21459214
  • Marashi A, Zazo A. Hybrid threshold laser to treat diabetic macular edema: A retrospective analysis single center cohort study. Ann Med Surg (Lond). 2022 Jul 31;80:104222. doi: 10.1016/j.amsu.2022.104222. eCollection 2022 Aug.

    PubMed 36045820

Questions about this trial

What is this clinical trial studying?

A study testing subthreshold treatment with micropulsed laser in people with Macular Edema and Inherited Retinal Dystrophy, run by Fondazione G.B. Bietti, IRCCS at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 28 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Lucia Ziccardi, MD, PhD (+390684009486, neuger@fondazionebietti.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

assessment of significative change in retinal oedema compared to baseline (time frame: up to 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05976139, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2025.

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